MICROSCAN SYNERGIES PLUS GRAM NEGATIVE MIC/COMBO PANELS WITH MOXIFLOXACIN (0.004-16UG/ML) by DADE BEHRING, INC.

The MicroScan Synergies plus" Gram-Negative MIC/Combo Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic Gram-Negative bacilli (Enterobacteriaceae, glucose non-fermenters, and non-Enterobacteriaceae glucose fermenters. After inoculation, panels are read on the WalkAway® SI System or equivalent (upgraded WalkAway® 40 or WalkAway® 96) according to the Package Insert.

This particular submission is for the antimicrobial Moxifloxacin on the Synergies plus™ Gram-Negative MIC/Combo Panels.

The Gram-Negative organisms which may be used for Moxifloxacin susceptibility testing in this panel are:

Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis

Device Description

MicroScan rapID/S plus ™ Gram-Negative MIC/Combo Panels are designed for use in determining quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-negative bacilli. The MicroScan rapID/S plus ™ Gram-Negative MIC/Combo Panels are read on the WalkAway® SI System or equivalent (upgraded WalkAway 40 or WalkAway® 96 instruments).

The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in Mueller-Hinton Broth to concentrations bridging the range of clinical interest and are presented in micro-titer wells in dried form. rapID/S plus ™ panels are inoculated and rehydrated with a standardized suspension of the organism and incubated at 35°C in the WalkAway® SI System or equivalent for 4.5 - 18 hours. The minimum inhibitory concentration (MIC) for the test organism is determined by the lowest antimicrobial concentration showing inhibition of growth.

AI/ML Overview

Here's an analysis of the provided text, focusing on the acceptance criteria and study information:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Typically for Antimicrobial Susceptibility Devices - from FDA Guidance mentioned in text)	Reported Device Performance (MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panel with Moxifloxacin)
Essential Agreement (EA): The MIC result of the device compared to the reference method is within one doubling dilution.	98.1% (518/528)
Categorical Agreement (CA): The interpretation (Susceptible, Intermediate, Resistant) of the device compared to the reference method matches.	97.7% (516/528)
Instrument Reproducibility	Acceptable reproducibility and precision (with Moxifloxacin, Turbidity inoculum, and WalkAway® SY System or equivalent)
Quality Control Testing	Acceptable results (for Moxifloxacin)

Study Details

Sample size used for the test set and the data provenance:
- Sample Size: 528 isolates
- Data Provenance: Not explicitly stated regarding country of origin. The test set consisted of "fresh and stock Efficacy isolates and stock Challenge strains." It is likely retrospective given the use of stock and challenge strains.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The ground truth was established by an "NCCLS frozen Reference Panel." This implies a standardized laboratory method rather than expert interpretation of individual cases. Therefore, the concept of "experts" in the traditional sense (e.g., radiologists) doesn't apply directly here. The NCCLS (now CLSI) standards are developed by committees of experts in microbiology.
Adjudication method for the test set:
- The method was a comparison to an "NCCLS frozen Reference Panel." This acts as the gold standard, so no additional adjudication (like 2+1, 3+1) was necessary for the test set results themselves.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No. This study is for an automated antimicrobial susceptibility system, not an AI-assisted diagnostic imaging device for human interpretation. Therefore, an MRMC study is not applicable.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes. The device (MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panel read on the WalkAway® SI System) operates as a standalone system. The results presented (Essential Agreement and Categorical Agreement) represent the performance of the device without human interpretation affecting the MIC determination. Human interaction would typically be involved in setting up the panels, but the reading and interpretation of the MIC are automated by the instrument.
The type of ground truth used:
- Reference method (NCCLS frozen Reference Panel). This is a highly standardized laboratory method considered the gold standard for antimicrobial susceptibility testing.
The sample size for the training set:
- Not explicitly stated in the provided text. The document describes the external evaluation which acts as the validation/test set. Details about the training set size for the underlying algorithm (if any, as this is an older device that likely relies on established biochemical reactions rather than deep learning) are not provided.
How the ground truth for the training set was established:
- Not explicitly stated. Given the nature of the device (antimicrobial susceptibility testing), it's highly probable that any implicit "training" or calibration of the system (e.g., interpreting growth patterns in wells) would be based on comparison to established reference methods (like those defined by NCCLS/CLSI) and a wide range of known isolates with confirmed resistance/susceptibility profiles.

Summary

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AUG 3 0 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Robert Eusebio Manager Regulatory Affairs Dade MicroScan. Inc. 1584 Enterprise Boulevard West Sacramento, CA 95691

Re: K023541 Trade/Device Name: MicroScan® Synergies Plus Gram Negative MIC/Combo Panels with Moxifloxacin (0.004 - 16 ug/ml) Regulation Number: 21 CFR 866.1645 Regulation Name: Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System Regulatory Class: II Product Code: LON Dated: July 30, 2004 Received: August 3, 2004

Dear Mr. Eusebio:

This letter corrects our substantially equivalent letter of December 13, 2002, regarding the trade name which was changed to MicroScan® Synergies Plus to better reflect the intended use of the device.

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent [(for the indications for use stated in the enclosure)] to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

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Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (sections 531-542 of the Act); 21 CFR 1000-1050.

This letter will allow you to continue marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally Part 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-3084. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at their toll free number (800) 638-2041 or at (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Freddie L. Hock for
Sally A. Hojvat, M.Sc., Ph.D.

Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement

510(k) Number (if known): K023541

MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels with Moxifloxacin Device Name: (0.004 - 16 ug/ml)

Indications For Use:

This particular submission is for the antimicrobial Moxifloxacin on the Synergies plus™ Gram-Negative MIC/Combo Panels.

The Gram-Negative organisms which may be used for Moxifloxacin susceptibility testing in this panel are:

Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis

Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Luddi tu-loole
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

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510(k) 02

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KO2354//

DEC 1 3 2002

510(k) Summary

510(k) Submission Information:

Device Manufacturer:	Dade Behring Inc.
Contact name:	Cynthia Van Duker, Manager Regulatory Affairs
Fax:	916-374-3144
Date prepared:	October 16, 2002
Product Name:	Microdilution Minimum Inhibitory Concentration (MIC) Panel
Trade Name:	MicroScan rapID/S plus™ Gram-Negative MIC/Combo panels
Intended Use:	To determine antimicrobial agent susceptibility
510(k) Notification:	Antimicrobials: Moxifloxacin
Predicate device:	MicroScan Dried Gram Negative MIC/Combo Panels

510(k) Summary:

The proposed MicroScan rapID/S plus™ Gram-Negative MIC/Combo Panel demonstrated substantially equivalent performance when compared with an NCCLS frozen Reference Panel, as defined in the FDA DRAFT document "Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices", dated March 8, 2000. The Premarket Notification (510/k/) presents data in support of the MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panel with Moxifloxacin.

The external evaluation was conducted with fresh and stock Efficacy isolates and stock Challenge strains. The external evaluations were designed to confirm the acceptability of the proposed rapID/S plus ™ Gram-Negative Panel by comparing its performance with an NCCLS frozen Reference panel. Challenge strains were compared to Frozen Results determined prior to the evaluation. The rapID/S plus™ Gram-Negative Panel demonstrated acceptable performance with an overall Essential Agreement of 98.1% (518/528), and a Categorical Agreement of 97.7% (516/528) compared with the frozen Reference panel.

Instrument reproducibility testing demonstrated acceptable reproducibility and precision with Moxifloxacin with Turbidity inoculum preparation method and the WalkAway® SY System or equivalent (upgraded WalkAway® 40 or WalkAway® 96 instruments).

Quality Control testing demonstrated acceptable results for Moxifloxacin.

Regulation Number and Section

§ 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system.

(a)
Identification. A fully automated short-term incubation cycle antimicrobial susceptibility system is a device that incorporates concentrations of antimicrobial agents into a system for the purpose of determining in vitro susceptibility of bacterial pathogens isolated from clinical specimens. Test results obtained from short-term (less than 16 hours) incubation are used to determine the antimicrobial agent of choice to treat bacterial diseases.(b)
Classification. Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA.”